What is the primary treatment for adrenal insufficiency?

Primary Treatment for Adrenal Insufficiency

The primary treatment for adrenal insufficiency consists of glucocorticoid replacement with hydrocortisone 15-25 mg daily in divided doses, plus mineralocorticoid replacement with fludrocortisone 50-200 μg daily for patients with primary adrenal insufficiency. 1, 2

Glucocorticoid Replacement

Hydrocortisone is the preferred glucocorticoid because it most closely mimics physiological cortisol and avoids the metabolic complications associated with synthetic glucocorticoids like prednisone 3, 1, 4.

Dosing Strategy

• Total daily dose: 15-25 mg hydrocortisone (or 18.75-31.25 mg cortisone acetate as an alternative) 3, 1
• Divide into 2-3 doses per day, with the most common schedule being: 10 mg upon waking + 5 mg at midday + 2.5 mg in the afternoon 1, 2
• First dose immediately upon waking to mimic the physiological cortisol peak 3, 1
• Last dose at least 6 hours before bedtime to avoid sleep disturbances 3, 1, 2
• In children: 6-10 mg/m² body surface area 3

The rationale for divided dosing is that current oral formulations cannot replicate the natural circadian rhythm of cortisol, and splitting doses attempts to provide more physiological coverage throughout the day 5.

Mineralocorticoid Replacement (Primary Adrenal Insufficiency Only)

Fludrocortisone 50-200 μg once daily is required for all patients with primary adrenal insufficiency 3, 1, 6. This is critical because primary adrenal insufficiency involves destruction of the entire adrenal cortex, resulting in aldosterone deficiency in addition to cortisol deficiency 7.

Key Points for Mineralocorticoid Therapy

• Children and younger adults may require higher doses (up to 500 μg daily) 1
• Advise patients to consume salt and salty foods without restriction 3, 1
• If essential hypertension develops, reduce but do not stop fludrocortisone; treat hypertension with vasodilators instead 3
• Avoid licorice and grapefruit juice, which can affect mineralocorticoid activity 3

Common pitfall: Chronic under-replacement with fludrocortisone combined with low salt intake predisposes patients to recurrent adrenal crises 8. This is a frequently missed cause of preventable morbidity.

Secondary Adrenal Insufficiency

Patients with secondary adrenal insufficiency require only glucocorticoid replacement (no fludrocortisone) because the renin-angiotensin-aldosterone system remains intact when the problem is at the pituitary level 7.

Stress Dosing and Adrenal Crisis Prevention

All patients must be educated on doubling or tripling their usual glucocorticoid dose during minor illnesses with fever 1, 9. This is non-negotiable for preventing adrenal crisis.

Emergency Preparedness

• Wear medical alert identification jewelry 3, 1, 2
• Carry a steroid emergency card 3, 9
• Possess supplies for self-injection of parenteral hydrocortisone 100 mg IM for use during vomiting or severe illness 3, 1, 9
• Receive training on when and how to administer emergency injections 9

Surgical Coverage

• Major surgery: 100 mg hydrocortisone IM before anesthesia, then 100 mg IM every 6 hours until oral intake resumes 1
• Minor surgery: 100 mg hydrocortisone IM before anesthesia, then double oral dose for 24 hours 1

Treatment of Acute Adrenal Crisis

Adrenal crisis requires immediate treatment with hydrocortisone 100 mg IV bolus, followed by 100 mg every 6-8 hours, plus rapid infusion of 0.9% saline at 1 L/hour initially 3, 1, 2, 8.

Critical Management Points

• Never delay treatment for diagnostic confirmation when adrenal crisis is suspected 2, 8
• Draw blood for cortisol and ACTH before treatment, but do not wait for results 8
• The 100 mg hydrocortisone dose provides adequate mineralocorticoid effect; do not add separate fludrocortisone during acute crisis 8
• Administer 3-4 liters of isotonic saline over 24 hours with frequent hemodynamic monitoring 1, 8
• Taper parenteral glucocorticoids over 1-3 days to oral maintenance therapy as the patient improves 1, 2, 8

Most common precipitating factors for adrenal crisis: gastrointestinal illness with vomiting/diarrhea, infections, and surgical procedures without adequate steroid coverage 1, 2, 8.

Monitoring and Follow-up

Annual follow-up should include assessment of weight, blood pressure, and serum electrolytes 3, 1, 2.

Signs of Inadequate Replacement

• Weight loss, fatigue, postural hypotension, salt craving, hyperpigmentation (in primary adrenal insufficiency) 1

Signs of Excessive Replacement

• Weight gain, hypertension, edema 1
• Monitor bone mineral density every 3-5 years to assess for complications of glucocorticoid therapy 3

Screen for Associated Autoimmune Conditions

• Check TSH, free T4, and TPO antibodies to screen for autoimmune thyroid disease 3, 2
• Check vitamin B12 levels to screen for autoimmune gastritis 1

Critical pitfall: Never start thyroid hormone replacement before adequate glucocorticoid replacement in patients with multiple hormone deficiencies, as this can precipitate adrenal crisis 8.